| Abstract: |
Naloxonazine is a relatively selective μ1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for μ1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistent inhibition of binding lasting 24 h which was relatively selective for μ1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both μ1 (naloxonazine-sensitive) and a non-μ1 (naloxonazine-insensitive) components. The ratio of μ1 to non-μ1 analgesia was greater at low morphine doses, implying that morphine activated μ1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively μ1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than μ1. © 1986. |
| Keywords: |
drug efficacy; nonhuman; mouse; animal; mice; animal experiment; central nervous system; drug receptor binding; kinetics; brain; rat; rats; drug blood level; radioisotope; morphine; analgesia; mu opiate receptor; drug binding; lethality; intravenous drug administration; pharmacokinetics; naloxone; opiate receptor; naloxonazine; morphine analgesia; rats, inbred strains; receptors, opioid; naloxazone; male; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalin[2 alanine 5 leucine] h 3; μ1 receptors; naloxonazine h 3
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